Although many observations have added to our knowledge of abnormalities in cystic fibrosis, these observations have produced only a few hints of the basic defect causing the disease. Based on recent studies of polyamine metabolism, one may tender an hypothesis to describe the disease process: (a) the basic defect in cystic fibrosis is an abnormality of polyamine metabolism; (b) the defect results in the elaboration of a toxic product, similar to a cystic fibrosis factor, and is a complex of a polyamine and protein; (c) this product affects membrane functions in various cells (sodium transport, excretion of mucus, ciliary motility). This hypothesis is offered to direct attention to one possible metabolic b@sis for the disease and to allow the gathering of relevant data. the hypothesis will be examined by studying polyamine metabolism in fibroblasts and patients, investigating possible similarities of polyamine-protein complexes with cystic fibrosis factors, and studying the effects of altered polyamine metabolism on other metabolic aber rations seen in cystic fibrosis patients and fibroblasts derived from them. The value of the hypothesis will lie in its ability to predict the pathophysiology seen in cystic fibrosis. From such knowledge, specific treatment for the basic defect may be possible.